Long non-coding RNA H19 regulates neurogenesis of induced neural stem cells in a mouse model of closed head injury

Stem cell-based therapies have been proposed as a potential treatment for neural regeneration following closed head injury.We previously reported that induced neural stem cells exert beneficial effects on neural regeneration via cell replacement.However,the neural regeneration efficiency of induced neural stem cells remains limited.In this study,we explored differentially expressed genes and long non-coding RNAs to clarify the mechanism underlying the neurogenesis of induced neural stem cells.We found that H19 was the most downregulated neurogenesis-associated lnc RNA in induced neural stem cells compared with induced pluripotent stem cells.Additionally,we demonstrated that H19 levels in induced neural stem cells were markedly lower than those in induced pluripotent stem cells and were substantially higher than those in induced neural stem cell-derived neurons.We predicted the target genes of H19 and discovered that H19 directly interacts with mi R-325-3p,which directly interacts with Ctbp2 in induced pluripotent stem cells and induced neural stem cells.Silencing H19 or Ctbp2 impaired induced neural stem cell proliferation,and mi R-325-3p suppression restored the effect of H19 inhibition but not the effect of Ctbp2 inhibition.Furthermore,H19 silencing substantially promoted the neural differentiation of induced neural stem cells and did not induce apoptosis of induced neural stem cells.Notably,silencing H19 in induced neural stem cell grafts markedly accelerated the neurological recovery of closed head injury mice.Our results reveal that H19 regulates the neurogenesis of induced neural stem cells.H19 inhibition may promote the neural differentiation of induced neural stem cells,which is closely associated with neurological recovery following closed head injury.

Induced neural stem cells regulate microglial activation through Akt-mediated upregulation of CXCR4 and Crry in a mouse model of closed head injury

Microglial activation that occurs rapidly after closed head injury may play important and complex roles in neuroinflammation-associated neuronal damage and repair.We previously reported that induced neural stem cells can modulate the behavior of activated microglia via CXCL12/CXCR4 signaling,influencing their activation such that they can promote neurological recovery.However,the mechanism of CXCR4 upregulation in induced neural stem cells remains unclear.In this study,we found that nuclear factor-κB activation induced by closed head injury mouse serum in microglia promoted CXCL12 and tumor necrosis factor-αexpression but suppressed insulin-like growth factor-1 expression.However,recombinant complement receptor 2-conjugated Crry(CR2-Crry)reduced the effects of closed head injury mouse serum-induced nuclear factor-κB activation in microglia and the levels of activated microglia,CXCL12,and tumor necrosis factor-α.Additionally,we observed that,in response to stimulation(including stimulation by CXCL12 secreted by activated microglia),CXCR4 and Crry levels can be upregulated in induced neural stem cells via the interplay among CXCL12/CXCR4,Crry,and Akt signaling to modulate microglial activation.In agreement with these in vitro experimental results,we found that Akt activation enhanced the immunoregulatory effects of induced neural stem cell grafts on microglial activation,leading to the promotion of neurological recovery via insulin-like growth factor-1 secretion and the neuroprotective effects of induced neural stem cell grafts through CXCR4 and Crry upregulation in the injured cortices of closed head injury mice.Notably,these beneficial effects of Akt activation in induced neural stem cells were positively correlated with the therapeutic effects of induced neural stem cells on neuronal injury,cerebral edema,and neurological disorders post–closed head injury.In conclusion,our findings reveal that Akt activation may enhance the immunoregulatory effects of induced neural stem cells on microglial activation via upregulation of CXCR4 and Crry,thereby promoting induced neural stem cell–mediated improvement of neuronal injury,cerebral edema,and neurological disorders following closed head injury.

Changes of Nitric Oxide and Its Relationship with Clinical Features,Intracranial Pressure and Outcome in Acute Head Injury

To investigate the content and dynamics of nitric oxide (NO) in the cerebrospinal fluid (CSF) of patients with acute head injury and to clarify the relationship of NO with clinical features and intracranial pressure (ICP) as well as outcomes, 38 adults with acute head injury were studied. Glasgow Coma Scale (GCS) obtained at admission and Glasgow Outcome Scale (GOS) 3 months after injury was assessed. ICP was surveyed via intraventricular catheter and lumbar puncture and CSF samples were obtained simultaneously. NO was determined with Griess reagents. Results showed that NO peak content in the head injury group was significantly higher than that of the control group. During dynamic research, no peak content of mildly injured cases and severely injured ones appeared in different time windows respectively. The peak value of NO was distinctly higher in the severe group than in the mild group. NO peak value of the raised ICP group was remarkably higher than that of the normal ICP group. The peak value of NO was considerately higher in the poor outcome group than in the good outcome group. When the content of NO was over 6. 5 μmol/L, the rate of poor outcome was increased. There existed a correlation between NO and GCS, ICP and GOS. It is concluded that the content of NO was increased in patients with acute head injury and the changes of NO had different time windows in severely injured patients and mildly injured ones. The more sever the injury, the higher the NO content; and the more serious the secondary brain injury and brain edema, the worse the outcomes. When NO is combined with GCS, GOS and ICP, it increases the accuracy of judgement to the degree of head injury and outcome.

Risk factors of posttraumatic cerebral infarction in patients with severe and extremely severe head injury

Objective To explore pathogenesis and risk factors for posttraumatic cerebral infarction (PTCI) in patients with severe and extremely severe head injuries for the purpose of providing clues for reducing occurrence of PTCI and case-fatality. Methods Gender,age,Glasgow coma scale (GCS) ,the presence or absence of basicranial fracture,cerebral hernia or infection,surgical modality,hypotension,and the use of diuretics

Comparative numerical study on the child head injury under different child safety seat angles

It has been shown that annually around 1250 children younger than 15 years old die in traffic accident.The number of children who also injured as a consequence of car accidents is noticeably higher.According to the ECE-R44 regulation the safety of children in the cars,the use of a child safety seat(CSS)is highly recommended.Using a CSS would dramatically diminish the injuries of traffic accidents.However,the posture,especially the angle,of a child when seating on a seat may also affect the amount of injury occurs during the accident.It has been revealed that during the accident only few children remained seated in the standard position,and most of them whether slouched or slanted and turned their head to the side-support of the CSS.Extreme positions,such as leaning forward,escaping from the harness or holding feet were also observed.This study aimed to perform a finite element(FE)study to figure out what angle of seating would result in the least amount of injury to the child head in a typical car crash under the speed of 47 km/h.To do that,a 1.5 years old child dummy(a dummy representing the anthropometry of a 1.5 years old child)has been accommodated on a seat under the angles of 15°,30°,and 45°.The results revealed.The resulted displacements in the head after the accident were also calculated at X,Y,and Z directions.The results in this regard indicated a higher displacement at X direction whereas the lowest one was seen at Y direction.The results have implications not only for understanding the amount of injury to the child head after the accident under different seating angles,but also for giving an insight to the CSS industries and families to choose the right seating posture for the child in the car to reduce the severity of injury.

An experimental and clinical study on TXA_2 and PGI_2 content after head injury

The correlation of secondary brain injury with thromboxane A2（TXA2） and prostacy-clin （PGI2） levels following head injury was studied in rats and patients.Thromboxane B2（TXB2） and 6-keto-PGF1α in rat brain homogenate and TXB2 in cerebral spinal fluid （CSF） ofpatients with severe head injury were determined by RIA.The effects of ligustrazini hydrochlo-rioi were also tested.The results showed that the concentration of TXB2 and 6-keto-PGF1α inrat brain was progressively increased within 3h after injury （P【0.01）,and the ratio betweenTXB2 and 6-keto-PGF1α（T/K value） increased during the early stage after injury,along withthe tissue damage aggravation.After the use of ligustrazini hydrochlorioi,TXB2 content inbrain decreased sharply accompanied with a drop in T/K value.Moreover,TXB2 content inCSF increased within 7 d after injury （P【0.01）,and it reached its peak value on the 3rd day.This could indicate that the metabolic imbalance between TXA2 and PGI2 might be one of theimportant factors in the development of secondary brain injury,and ligustrazini hydrochlorioiproved to have a protective effect on the brain tissue by normalizing the metabolism of TXA2and PGI2.In addition,the metabolic disorders of TXA2 in the brain tissue of head injured pa-tients have much to do with the outcome of the patients.

Significance of computed tomography scans in head injury

Background: In view of the growing population and increased vehicle use, traumatic brain injury is becoming the most common and devastating problem especially in young healthy people. It has occupied second place next to cancer as leading cause of death. In this new era of radiology, computed tomography has become the primary modality of choice in the initial assessment of head injury patients as it is widely available, faster and highly accurate in detecting skull fractures and acute intracranial hemorrhage. Aim: It is to demonstrate the importance of ct scanning in the initial treatment planning, follow up and long term management of patients with acute head injury of varying severity. Patients: A retrospective study has been carried out of 100 cases of acute head trauma with positive CT scanning referred to Narayana medical college and hospital, Nellore, India between 30th April 2012 to 1st May 2013 [1 year retrospective study]. Results: The post traumatic intracranial consequences have been collected, reviewed and analyzed, where in 82% of cases males were involved , and most of the injured people belong to the first three decades of life, the main cause being road traffic accident which is growing in incidence in this 21st century. Most of the cases which were studied showed skull fractures, which indicates that there has been significant trauma and in a single case more than one pathology related to cranium has been seen. The most common post traumatic consequences found in the study of adults are contusions, brain edema and intracerebral hematomas, while other sequelae such as subarachnoid hematomas, subdural hematomas and extradural hematomas are encountered less. Diffuse and focal cerebral edema was being the most common pathology following trauma in children. Conclusion: CT scanning is the primary modality of choice in the diagnostic work up of patients with acute head trauma for identifying the various intracranial consequences following head injury especially within 48 hours which helps in the initial assessment, treatment planning, follow up and long term management of patients.

Effects of thyrotropin-releasing hormone on severe head injury:A preliminary clinical trial

Objective: To evaluate the effects of thyorotropin-releasing hormone (TRH ) on severe head injury.Methods: Eighty--seven severely head injured patients with a Glasgow Coma Scale (GCS ) score of & or less wererandomized into TRH--treated and saline control groups. In TRH treated group. the treatment was started with abolus injection of 0. 2 mg/kg followed by continuous infusion for 2 hours at 0. 2 mg/kg/h. Such treatment wasgiven once a day for 4 times. The patients in control group were given the equivalent normal saline with the samemethod. Results: TRH, administered intravenously after head injury. promoted the recovery of consciousness andGCS score, alleviated the traumatic brain edema, controlled and lowered the intracranial pressure. decreased thelevel of lipid superoxides, decreased the mortality rate. and improved the life quality of the survivals. Nocomplications or adverse and toxic effects were noted during the course of TRH treatment. Conclusion: TRH hasbeneficial effects on patients with severe head injury.

Early enteral nutrition supplemented with probiotics improved the clinical outcomesin patients with severe head injury： protocol for a meta-analysis of randomizedcontrolled trials

目的：探讨添加益生菌的早期肠内营养对重型颅脑损伤患者临床结局的影响.方法：电子检索PubMed、Cochrane CentralRegister of Controlled Trials（CENTRAL）、中国知网（China National Knowledge Infrastructure,CNKI）、万方及中国生物医学文献数据库（Chinese Biomedical Literature Database,CBM）中有关添加益生菌的早期肠内营养对重型颅脑损伤患者临床结局影响的随机对照研究（Randomizedcontrolledtrials,RCTs）,并手工检索合格研究及主题相关综述的参考文献.2位研究者独立筛查文献、提取资料、评价合格研究的偏倚风险后,采用STATA12.0软件行Meta分析.伦理与发布：本研究所有分析均基于已发表研究中所报告数据,因此不需要签署伦理许可和患者知情同意书.本系统评价全文完成后,将发表于同行评审的期刊杂志.

Fetal Head Compression: Its Possible Role in Neurologic Injury

It is widely assumed that fetal ischemic brain injury during labor derives almost exclusively from severe, systemic hypoxemia with marked neonatal depression and acidemia. Severe asphyxia, however, is one of several causes of perinatal neurological injury and may not be the most common;most neonates diagnosed with hypoxic-ischemic encephalopathy do not have evidence of severe asphyxia. Sepsis, direct brain trauma, and drug or toxin exposure account for some cases, while mechanical forces of labor and delivery that increase fetal intracranial pressure sufficiently to impair brain perfusion may also contribute. Because of bony compliance and mobile suture lines, the fetal skull changes shape and redistributes cerebrospinal fluid during labor according to constraints imposed by contractions, and bony and soft tissue elements of the birth canal as the head descends. These accommodations, including the increase in intracranial pressure, are adaptive and necessary for efficient descent of the head while safeguarding cerebral blood flow. Autonomic reflexes mediated through central receptors normally provide ample protection of the brain from the considerable pressure exerted on the skull. On occasion, those forces, which are transmitted intracranially, may overcome the various adaptive anatomical, cardiovascular, metabolic, and neurological mechanisms that maintain cerebral perfusion and oxygen availability, resulting in ischemic brain injury. Accepting the notion of a potentially adverse impact of fetal head compression suggests that avoidance of excessive uterine activity and of relentless pushing without steady progress in descent may offer protection for the fetal brain during parturition. Excessive head compression should be considered in the differential diagnosis of ischemic encephalopathy.

Knowledge, Attitude, and Practice of Using Helmets in Children amongst Parents to Prevent Head Injuries: A Cross-Sectional Study in Riyadh, Saudi Arabia

Objectives: The primary objective was to characterize the range of Knowledge, Attitude, and Practice (KAP) of Helmet use in children amongst parents to prevent head injuries and death. Methods: This is a cross-sectional study, done by online survey using a snowball sampling technique, the number of included responses were 386 parents (Male and female) living in Riyadh Aged 21 - 60 years old or above. Results: The study showed that there is a difference in Parents’ belief in the importance of helmet use while riding a Bicycle vs Motorcycle/Quad bike and that was affected by parents’ education level, almost all the people who answered the survey (76.7%) agree that it is important for their children to wear a helmet when riding both a Bicycle and a Motorcycle or Quadbike with a cumulative percentage of (93.8%). And almost all agreed on multiple approaches to help increase helmet use be it by forcing rental shops to give out helmets, forcing sellers to recommend the use of helmets, increasing awareness campaigns, and imposing fines for not wearing helmets. Conclusions: This study is the first to explore Family helmet use while riding Bicycles and Motorcycles/Quad bikes. Although Parent’s belief in the importance of helmet use for their children was high, it is clear that the level of practice is low. With that the risk of head injuries might be high, our findings suggest that safety interventions for increasing pediatric helmet use are needed to increase helmet use and reduce the risk of head injury and hospitalization.

Severe Cut Throat Injury in a Child: A Case Report and Review of Literature

Background: Cut-throat injury is a potentially fatal condition that may be associated with serious morbidity and mortality. The neck region is particularly at risk of serious injuries due to the location of vital structures, including nerves, viscera, and major vessels. Although cut-throat injury is said to be rare in children, its occurrence has been reported in some series. Management of this condition requires a multidisciplinary approach for a better outcome. Aim: The aim of this report is to highlight the successful management of an alarming case of severe cut-throat injury with associated laryngeal injury in a child. Case presentation: A 12-year-old boy presented with a cut-throat following an assault by an unknown person. Examination revealed an acutely ill child, conscious but pale. He sustained a deep transverse laceration that transected the thyroid cartilage, exposing the laryngeal cavity. An assessment of Zone II penetrating neck injury was made. He was resuscitated, and had emergency neck exploration, tracheostomy, and repair of the injuries. The patient was followed up for 6 months, and had a good voice outcome, with no significant complication. Conclusion: Cut-throat injury is rare in children. But it is a potentially life-threatening condition. It is therefore important to recognize this entity and develop effective protocol of management in our environment.

dl-3-n-butylphthalide reduces brain damage in mice with closed head injury

To investigate the protective effect of dl 3 n butylphthalide (NBP) as an anti cerebral ischemic drug on brain damage 24?h after closed head injury in mice Methods Closed head injury was induced by dropping a 50 g weight from a height of 18?cm on a metal impounder resting on the parietal bone in mice Results The neurotraumatic model induced impair^ment of memory function, significant cerebral edema, and disruption of the blood brain barrier dl 3 n butylphthalide (50?mg·kg 1 ) given intraperitoneally 5 minutes and 60 minutes after the onset of closed head injury was found to attenuate the impairment of memory function ( P <0 05), alleviate brain edema in the injured cerebral cortex ( P <0 05), and reduce extravasation of plasma protein bound to Evans blue dye by 63 5% ( P <0 01) NBP was also shown to increase the activity of choline acetyltransferase in the injured cortex to 0 83±0 21?ng·min 1 ·mg 1 ( P <0 01, compared with 0 48±0 14?ng·min 1 ·mg 1 of vehicle group) Conclusion NBP provides therapeutic response in experimental closed head injury

Rational design of secondary operation for penetrating head injury:A case report

Penetrating head injury is rare,and thus management of such injuries is non-standard.Early diagnosis and intraoperative comprehensive exploration are necessary considering the complexity and severity of the trauma.However,because of the lack of microsurgical techniques in local hospitals,the possible retained foreign bodies and other postoperative complications such as cerebrospinal fluid(CSF)leak usually require a rational design for a secondary operation to deal with.We present a case of a 15-year-old boy who was stabbed with a bamboo stick in his left eye.The chopsticks passed through the orbit roof and penetrated the skull base.In subsequent days,the patient sustained CSF leak and intracranial infection after an unsatisfied primary treatment in the local hospital and had to request a secondary operation in our department.Computed tomography including plain scan,three dimension recon-struction and computed tomographic angiography are used to determine the course and extent of head injury.A frontal craniotomy was performed.Three pieces of stick were found residual and removed with the comminuted orbit bone fragments.A pedicled temporalis muscle fascia graft was applied to repair the frontier skull base and a free temporalis muscle flap to seal the frontal sinus defect.Aggressive broad-spectrum antibiotics of vancomycin and meropenem were administrated for persistent fever after operation.CSF external drainage system continued for 12 days,and was removed 10 days after tem-perature returned to normal.The Glasgow coma scale score was improved to 15 at postoperative day 7 and the patient was discharged at day 22 uneventfully.We believe that appropriate preoperative surgical plan and thorough surgical exploration by microsurgery is essential for attaining a favorable outcome,especially in secondary operation.Good postoperative recovery depends on successfully management before and after operation for possible complications as well.

Development of a symptom expectation questionnaire for minor head injury

Background and objective:Expectations and beliefs are important predictors of outcome following minor head injury.In this paper,the primary purpose is to develop a simple symptom expectation questionnaire for minor head injury for use in future research studies.Methods:An existing database of 179 injury-naive subjects who completed a 56-item checklist of expected symptoms for minor head injury was analyzed to determine which items could correctly identify an a priori case definition of an expecter (a subject who expected at least one of these symptoms would remain chronic following minor head injury).A total of six of the 56 items were found to be discriminatory,and these were tested in additional subject groups against the original questionnaire.Results:From the original database of 179 subjects completing a 56-item symptom expectation checklist,135 expected that at least one of the 56 symptoms would be chronic following minor head injury.The 135 expecters,however,all chose at least one of six items:headache,anxious or worried,depressed,difficulty concentrating,dizziness,and neck pain.Using these six items,in two new groups of subjects,all those who endorsed one of the 56 symptoms as likely to be chronic following minor head injury (expecters) could also be identified on the 6-item checklist.Conclusions:A shortened (6-item) symptom expectation checklist of commonly reported symptoms following minor head injury (headache,anxious or worried,depressed,difficulty concentrating,dizziness,and neck pain) correctly identifies subjects who expect that at least one symptom will be chronic following minor head injury (i.e.,an expecter).

Chronic subdural haematoma during the COVID-19 lockdown period:late presentation with a longer interval from the initial head injury to the final presentation and diagnosis

Background:The COVID-19 novel coronavirus is contagious,and the mortality is higher in the elderly population.Lockdown in different parts of the world has been imposed since January 2020.Chronic subdural haematoma (cSDH) has a unique natural history in which symptoms can be non-specific,and the onset is insidious.This study aims to evaluate the impact of the COVID-19 pandemic on the presentation of cSDH.Methods:Consecutive adult cSDH patients admitted from 1 March 2020 to 30 April 2020 were reviewed.Exclusion criteria including those who had no definite history of head injury or the diagnosis of cSDH were made from a scheduled follow-up scan.Corresponding data during the same period in 2019 were reviewed for comparison.The primary outcome was the interval between the initial head injury and the final radiological diagnosis of cSDH.Secondary outcomes include Markwalder chronic subdural haematoma grade upon admission,length of stay in the acute hospital,and the modified Rankin scale (mRS) upon discharge.Results:For the primary outcome,the average interval between head injury and the diagnosis of cSDH was significantly longer at 56.6 days (49 to 74 days,SD 9.83 days) during the period from March to April 2020,versus 29.4 days (17 to 42 days,SD 8.59 days) in 2019 for the corresponding period (p = 0.00703).There was no significant difference in the functional outcome upon discharge.Conclusions:cSDH patients can present late during the COVID-19 lockdown period.The functional outcome was comparable when operations for drainage were timely performed.

Clinical studies on diffuse axonal injury in patients with severe closed head injury

OBJECTIVE: To discuss the clinical criteria for diagnosing diffuse axonal injury (DAI). METHODS: Clinical and computed tomographic features of 117 patients with severe closed head injury were analyzed. The authors preliminarily put forward CT diagnostic criteria of DAI, that is, 1) single or multiple small intraparenchymal hemorrhages in the cerebral hemispheres (

The usefulness of diffusion tensor imaging in detection of diffuse axonal injury in a patient with head trauma

Diffuse axonal injury is the predominant mechanism of injuries in patients with traumatic brain injury. Neither conventional brain computed tomography nor magnetic resonance imaging has shown sufficient sensitivity in the diagnosis of diffuse axonal injury. In the current study, we attempted to demonstrate the usefulness of diffusion tensor imaging in the detection of lesion sites of diffuse axonal injury in a patient with head trauma who had been misdiagnosed as having a stroke. A 44-year-old man fell from a height of about 2 m. Brain magnetic resonance imaging （32 months after onset） showed leukomalactic lesions in the isthmus of the corpus callosum and the left temporal lobe. He presented with mild quadriparesis, intentional tremor of both hands, and trunkal ataxia. From diffusion tensor imaging results of 33 months after traumatic brain injury onset, we found diffuse axonal injury in the right corticospinal tract （centrum semiovale, pons）, both fomices （columns and crus）, and both inferior cerebellar peduncles （cerebellar portions）. We think that diffusion tensor imaging could be a useful tool in the detection of lesion sites of diffuse axonal injury in patients with head trauma.

Study of the effects of mild hypothermia on cerebral PO_2, PCO_2 and pH and body temperature in patients with acute severe head injury

Objective: To study the effects of mild hypothermia on cerebral oxygen partial pressure, carbon dioxide partial pressure, pH and body temperature （PbrO2, PbrCO2, pHbr and BT） in patients with acute severe head injury. Methods: Thirty-eight patients with acute severe head injury were treated with mild hypothermia, meantime PbrO2, PbrCO2, pHbr and BT were monitored in order to study the changes of PbrO2, PbrCO2, pHbr and BT. Results: In patients with acute head injury, mild hypothermia obviously increased PbrO2, decreased PbrCO2 and CO2 accumulation and acidosis in brain tissue. BT was 1℃-（1.5）℃ higher than rectal temperature（RT） after injury. The BT and RT were decreased when the patients were treated with mild hypothermia, but at the same time the difference between BT and RT was increased. Conclusions: In patients with acute severe head injury the direct monitoring of PbrO2, PbrCO2, pHbr and BT was safe and reliable, and is helpful in estimating prognosis and mild hypothermia therapy.

Moderate hypothermia therapy for patients with severe head injury

Objective: To evaluate the effect and safety of early moderate hypothermia therapy (MHT) on patients with head injury by using parallel control test. Methods: Thirty patients with severe head injury within 6 hours after accidents were treated by MHT generally for 4 10 days. The other 30 patients with similar head injury treated routinely were enrolled for a parallel control test. The mortality, morbidity and changes of some neuro functional indexes as Glasgow Coma Scores, and Glasgow Outcome Scale, levels of endothelin and some other factors of neurobiochemistry in blood plasma were observed. Meanwhile, the dynamic monitoring by transcranial Doppler ultrasonography was conducted in these patients. Results: The mortality in MHT group was significantly lower than that in control group. MHT not only reduced endothelin but also increased the brain biochemical factors, which were helpful to the protection of neurons in the early brain ischemia after head injury. Conclusions: Early MHT can help reduce mortality and morbidity in patients with acute head injury.